We will use the X-ray crystallographic method to determine the three-dimensional structure of the penicillin-destroying beta-lactamase enzyme (penicillinase) encoded by the infectious R-TEM plasmid. We will examine crystalline complexes between the enzyme and beta-lactams (penicillins and cephalosporins) or related analogs to define the stereochemistry of the binding and hydrolysis of these antibiotics to inactive penicilloic acids. We hope to provide conformational information for the rational design of beta-lactamase-resistant penicillins or for beta-lactamase inhibitors.